ترغب بنشر مسار تعليمي؟ اضغط هنا

Personalized Dynamic Treatment Regimes in Continuous Time: A Bayesian Approach for Optimizing Clinical Decisions with Timing

132   0   0.0 ( 0 )
 نشر من قبل Yanxun Xu
 تاريخ النشر 2020
  مجال البحث الاحصاء الرياضي
والبحث باللغة English




اسأل ChatGPT حول البحث

Accurate models of clinical actions and their impacts on disease progression are critical for estimating personalized optimal dynamic treatment regimes (DTRs) in medical/health research, especially in managing chronic conditions. Traditional statistical methods for DTRs usually focus on estimating the optimal treatment or dosage at each given medical intervention, but overlook the important question of when this intervention should happen. We fill this gap by developing a two-step Bayesian approach to optimize clinical decisions with timing. In the first step, we build a generative model for a sequence of medical interventions-which are discrete events in continuous time-with a marked temporal point process (MTPP) where the mark is the assigned treatment or dosage. Then this clinical action model is embedded into a Bayesian joint framework where the other components model clinical observations including longitudinal medical measurements and time-to-event data conditional on treatment histories. In the second step, we propose a policy gradient method to learn the personalized optimal clinical decision that maximizes the patient survival by interacting the MTPP with the model on clinical observations while accounting for uncertainties in clinical observations learned from the posterior inference of the Bayesian joint model in the first step. A signature application of the proposed approach is to schedule follow-up visitations and assign a dosage at each visitation for patients after kidney transplantation. We evaluate our approach with comparison to alternative methods on both simulated and real-world datasets. In our experiments, the personalized decisions made by the proposed method are clinically useful: they are interpretable and successfully help improve patient survival.

قيم البحث

اقرأ أيضاً

78 - Shuxiao Chen , Bo Zhang 2021
Estimating dynamic treatment regimes (DTRs) from retrospective observational data is challenging as some degree of unmeasured confounding is often expected. In this work, we develop a framework of estimating properly defined optimal DTRs with a time- varying instrumental variable (IV) when unmeasured covariates confound the treatment and outcome, rendering the potential outcome distributions only partially identified. We derive a novel Bellman equation under partial identification, use it to define a generic class of estimands (termed IV-optimal DTRs), and study the associated estimation problem. We then extend the IV-optimality framework to tackle the policy improvement problem, delivering IV-improved DTRs that are guaranteed to perform no worse and potentially better than a pre-specified baseline DTR. Importantly, our IV-improvement framework opens up the possibility of strictly improving upon DTRs that are optimal under the no unmeasured confounding assumption (NUCA). We demonstrate via extensive simulations the superior performance of IV-optimal and IV-improved DTRs over the DTRs that are optimal only under the NUCA. In a real data example, we embed retrospective observational registry data into a natural, two-stage experiment with noncompliance using a time-varying IV and estimate useful IV-optimal DTRs that assign mothers to high-level or low-level neonatal intensive care units based on their prognostic variables.
One of the main goals of sequential, multiple assignment, randomized trials (SMART) is to find the most efficacious design embedded dynamic treatment regimes. The analysis method known as multiple comparisons with the best (MCB) allows comparison bet ween dynamic treatment regimes and identification of a set of optimal regimes in the frequentist setting for continuous outcomes, thereby, directly addressing the main goal of a SMART. In this paper, we develop a Bayesian generalization to MCB for SMARTs with binary outcomes. Furthermore, we show how to choose the sample size so that the inferior embedded DTRs are screened out with a specified power. We compare log-odds between different DTRs using their exact distribution without relying on asymptotic normality in either the analysis or the power calculation. We conduct extensive simulation studies under two SMART designs and illustrate our methods application to the Adaptive Treatment for Alcohol and Cocaine Dependence (ENGAGE) trial.
In clinical practice, physicians make a series of treatment decisions over the course of a patients disease based on his/her baseline and evolving characteristics. A dynamic treatment regime is a set of sequential decision rules that operationalizes this process. Each rule corresponds to a decision point and dictates the next treatment action based on the accrued information. Using existing data, a key goal is estimating the optimal regime, that, if followed by the patient population, would yield the most favorable outcome on average. Q- and A-learning are two main approaches for this purpose. We provide a detailed account of these methods, study their performance, and illustrate them using data from a depression study.
There is a fast-growing literature on estimating optimal treatment regimes based on randomized trials or observational studies under a key identifying condition of no unmeasured confounding. Because confounding by unmeasured factors cannot generally be ruled out with certainty in observational studies or randomized trials subject to noncompliance, we propose a general instrumental variable approach to learning optimal treatment regimes under endogeneity. Specifically, we establish identification of both value function $E[Y_{mathcal{D}(L)}]$ for a given regime $mathcal{D}$ and optimal regimes $text{argmax}_{mathcal{D}} E[Y_{mathcal{D}(L)}]$ with the aid of a binary instrumental variable, when no unmeasured confounding fails to hold. We also construct novel multiply robust classification-based estimators. Furthermore, we propose to identify and estimate optimal treatment regimes among those who would comply to the assigned treatment under a standard monotonicity assumption. In this latter case, we establish the somewhat surprising result that complier optimal regimes can be consistently estimated without directly collecting compliance information and therefore without the complier average treatment effect itself being identified. Our approach is illustrated via extensive simulation studies and a data application on the effect of child rearing on labor participation.
468 - Jiuyong Li , Saisai Ma , Lin Liu 2019
In personalised decision making, evidence is required to determine suitable actions for individuals. Such evidence can be obtained by identifying treatment effect heterogeneity in different subgroups of the population. In this paper, we design a new type of pattern, treatment effect pattern to represent and discover treatment effect heterogeneity from data for determining whether a treatment will work for an individual or not. Our purpose is to use the computational power to find the most specific and relevant conditions for individuals with respect to a treatment or an action to assist with personalised decision making. Most existing work on identifying treatment effect heterogeneity takes a top-down or partitioning based approach to search for subgroups with heterogeneous treatment effects. We propose a bottom-up generalisation algorithm to obtain the most specific patterns that fit individual circumstances the best for personalised decision making. For the generalisation, we follow a consistency driven strategy to maintain inner-group homogeneity and inter-group heterogeneity of treatment effects. We also employ graphical causal modelling technique to identify adjustment variables for reliable treatment effect pattern discovery. Our method can find the treatment effect patterns reliably as validated by the experiments. The method is faster than the two existing machine learning methods for heterogeneous treatment effect identification and it produces subgroups with higher inner-group treatment effect homogeneity.
التعليقات
جاري جلب التعليقات جاري جلب التعليقات
سجل دخول لتتمكن من متابعة معايير البحث التي قمت باختيارها
mircosoft-partner

هل ترغب بارسال اشعارات عن اخر التحديثات في شمرا-اكاديميا